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Lasers in Medical Science May 2024Conventional approaches for enhancing wound healing may not always yield satisfactory results. Instead, we test the effectiveness of a newly developed photodynamic...
PURPOSE
Conventional approaches for enhancing wound healing may not always yield satisfactory results. Instead, we test the effectiveness of a newly developed photodynamic therapy (PDT) that uses methylene blue (MB) loaded with polyethylene glycol (PEG) (MB-PEG) hydrogel to accelerate wound healing process in mice.
METHODS
A dorsal skin incision with 6 mm punch which topically subjected to MB-PEG hydrogel and a low-level laser light of red light to assess the regeneration process of wounded skin. A total of 63 adult male CD1 mice divided into normal group (no treatment) and other wound groups received different treatments of laser (650 ± 5 nm and power intensity of 180 mW/cm), MB-PEG, or PDT (MB-PEG followed by laser). The wound healing parameters were investigated by histological examination of the skin and measuring of proinflammatory cytokines at the early stage (48 h) and a late one on day 21.
RESULTS
at 48 h, the score of tissue granulation, inflammation, and angiogenesis process were markedly improved in wounded groups that received MB + PEG combined with laser compared to the group treated with laser alone. On day 21, a significant improvement of the inflammation was detected in the group treated with MB + PEG plus laser compared to the other groups. At 48 h, the upregulated serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the wound group were significantly (P < 0.001) reduced in the group treated with MB + PEG combined with laser.
CONCLUSION
MB-PEG based hydrogel improves and accelerates wound closure in the context of laser compared to either single treatment.
Topics: Animals; Wound Healing; Mice; Photochemotherapy; Polyethylene Glycols; Methylene Blue; Male; Skin; Hydrogels; Photosensitizing Agents; Cytokines
PubMed: 38801600
DOI: 10.1007/s10103-024-04084-1 -
Advances in Radiation Oncology Jul 2024Current standard of care treatment for patients with ≥15 brain metastases (BM) is whole brain radiation therapy (WBRT), despite poor neurocognitive outcomes. We...
BACKGROUND
Current standard of care treatment for patients with ≥15 brain metastases (BM) is whole brain radiation therapy (WBRT), despite poor neurocognitive outcomes. We analyzed our institutional experience of treating these patients with stereotactic radiosurgery (SRS), with the aim of evaluating safety, cognitive outcomes, and survival metrics.
METHODS
Patients who received SRS for ≥15 BMs in 1 to 5 fractions from 2014 to 2022 were included. Cognitive outcomes were objectively evaluated using serial Patient-Reported Outcome Measurement Information System (PROMIS) scores. The Kaplan-Meier method was used for survival analysis and log-rank test for intergroup comparisons.
RESULTS
Overall, 118 patients underwent 124 courses of LINAC-based SRS. The median number of lesions treated per course was 20 (range, 15-94). Most patients received fractionated SRS to a dose of 24 Gy in 3 fractions (81.5%). At the time of SRS, 19.4% patients had received prior WBRT, and 24.2% had received prior SRS. The rate of any grade radiation necrosis (RN) and grade ≥3 RN were 15.3% and 3.2%, respectively. When evaluating longitudinal PROMIS score trends, 25 of 31 patients had a stable/improved PROMIS score. Patients who did not receive prior brain RT had a longer median survival (7.4 months vs 4.6 months, = .034). The 12m local control was 97.6%, and the cumulative incidence of distant intracranial failure, with death as a competing event, was 46% (95% CI, 36%, 55%). One year freedom from neurologic death, leptomeningeal disease, and salvage WBRT were 89%, 94.6%, and 84%, respectively.
CONCLUSION
We present here one of the largest studies evaluating SRS for patients with ≥15 BMs. SRS was safe, had favorable cognitive outcomes, and had comparable survival outcomes to contemporary studies evaluating WBRT in this population. Treatment-naïve patients had a median survival of >6 months, long enough to benefit from cognitive sparing with SRS. Our study supports randomized studies comparing SRS and hippocampal avoidance WBRT approaches for these patients.
PubMed: 38799108
DOI: 10.1016/j.adro.2024.101509 -
BMC Neuroscience May 2024The challenge of treating Glioblastoma (GBM) tumors is due to various mechanisms that make the tumor resistant to radiation therapy. One of these mechanisms is hypoxia,...
INTRODUCTION
The challenge of treating Glioblastoma (GBM) tumors is due to various mechanisms that make the tumor resistant to radiation therapy. One of these mechanisms is hypoxia, and therefore, determining the level of hypoxia can improve treatment planning and initial evaluation of its effectiveness in GBM. This study aimed to design an intelligent system to classify glioblastoma patients based on hypoxia levels obtained from magnetic resonance images with the help of an artificial neural network (ANN).
MATERIAL AND METHOD
MR images and PET measurements were available for this study. MR images were downloaded from the Cancer Imaging Archive (TCIA) database to classify glioblastoma patients based on hypoxia. The images in this database were prepared from 27 patients with glioblastoma on T1W + Gd, T2W-FLAIR, and T2W. Our designed algorithm includes various parts of pre-processing, tumor segmentation, feature extraction from images, and matching these features with quantitative parameters related to hypoxia in PET images. The system's performance is evaluated by categorizing glioblastoma patients based on hypoxia.
RESULTS
The results of classification with the artificial neural network (ANN) algorithm were as follows: the highest sensitivity, specificity, and accuracy were obtained at 86.71, 85.99 and 83.17%, respectively. The best specificity was related to the T2W-EDEMA image with the tumor to blood ratio (TBR) as a hypoxia parameter. T1W-NECROSIS image with the TBR parameter also showed the highest sensitivity and accuracy.
CONCLUSION
The results of the present study can be used in clinical procedures before treating glioblastoma patients. Among these treatment approaches, we can mention the radiotherapy treatment design and the prescription of effective drugs for the treatment of hypoxic tumors.
Topics: Humans; Glioblastoma; Magnetic Resonance Imaging; Brain Neoplasms; Neural Networks, Computer; Female; Male; Middle Aged; Hypoxia; Positron-Emission Tomography; Algorithms; Aged; Adult
PubMed: 38789970
DOI: 10.1186/s12868-024-00871-2 -
Frontiers in Immunology 2024While radiotherapy has long been recognized for its ability to directly ablate cancer cells through necrosis or apoptosis, radiotherapy-induced abscopal effect suggests...
INTRODUCTION
While radiotherapy has long been recognized for its ability to directly ablate cancer cells through necrosis or apoptosis, radiotherapy-induced abscopal effect suggests that its impact extends beyond local tumor destruction thanks to immune response. Cellular proliferation and necrosis have been extensively studied using mathematical models that simulate tumor growth, such as Gompertz law, and the radiation effects, such as the linear-quadratic model. However, the effectiveness of radiotherapy-induced immune responses may vary among patients due to individual differences in radiation sensitivity and other factors.
METHODS
We present a novel macroscopic approach designed to quantitatively analyze the intricate dynamics governing the interactions among the immune system, radiotherapy, and tumor progression. Building upon previous research demonstrating the synergistic effects of radiotherapy and immunotherapy in cancer treatment, we provide a comprehensive mathematical framework for understanding the underlying mechanisms driving these interactions.
RESULTS
Our method leverages macroscopic observations and mathematical modeling to capture the overarching dynamics of this interplay, offering valuable insights for optimizing cancer treatment strategies. One shows that Gompertz law can describe therapy effects with two effective parameters. This result permits quantitative data analyses, which give useful indications for the disease progression and clinical decisions.
DISCUSSION
Through validation against diverse data sets from the literature, we demonstrate the reliability and versatility of our approach in predicting the time evolution of the disease and assessing the potential efficacy of radiotherapy-immunotherapy combinations. This further supports the promising potential of the abscopal effect, suggesting that in select cases, depending on tumor size, it may confer full efficacy to radiotherapy.
Topics: Humans; Neoplasms; Immunotherapy; Combined Modality Therapy; Models, Theoretical; Radiotherapy
PubMed: 38779678
DOI: 10.3389/fimmu.2024.1373738 -
Monilinia fructicola genes involved in the cell wall-degrading process in early nectarine infection.International Journal of Food... Jul 2024Brown rot symptoms may be linked to alterations in the gene expression pattern of genes associated with cell wall degradation. In this study, we identify key...
Brown rot symptoms may be linked to alterations in the gene expression pattern of genes associated with cell wall degradation. In this study, we identify key carbohydrate-active enzymes (CAZymes) involved in cell wall degradation by Monilinia fructicola, including pme2 and pme3 (pectin methylesterases), cut1 (cutinase) and nep2 (necrosis-inducing factor). The expression of these genes is significantly modulated by red and blue light during early nectarine infection. The polygalacturonase gene pg1 and the cellulase gene cel1 also exhibit photoinduction albeit to a lesser extent. Red and blue light cause an acceleration in the initial stages of brown rot development caused by M. fructicola on nectarines. Disease symptoms like tissue maceration were evident after an incubation period of 24 h followed by 14 h of light exposition, in contrast to the usual incubation period of 48 to 72 h. Furthermore, the culture media exerts an impact on gene regulation, suggesting a complex interplay between light and nutrient signalling pathways in M. fructicola. In addition, we observe that red light promotes colony growth on a 12 h photoperiod and consistently reduces conidiation. In contrast, blue light hampers growth rate on both the 12 h and the 8 h photoperiod but only diminishes conidiation on the 12 h photoperiod. These findings enhance our comprehension of genes associated with cell wall degradation and the environmental factors influencing brown rot development.
Topics: Cell Wall; Ascomycota; Plant Diseases; Light; Gene Expression Regulation, Fungal; Fungal Proteins
PubMed: 38776709
DOI: 10.1016/j.ijfoodmicro.2024.110750 -
Inflammation May 2024Cancer therapy has entered a new era with the use of programmed cell death protein 1 (PD-1) immune checkpoint inhibitors. When combined with thoracic radiotherapy, it...
Cancer therapy has entered a new era with the use of programmed cell death protein 1 (PD-1) immune checkpoint inhibitors. When combined with thoracic radiotherapy, it demonstrates synergistic anti-tumor effects and potentially worsens radiation-induced myocardial fibrosis (RIMF). RIMF is the final stage of radiation-induced heart disease (RIHD) and a potentially fatal clinical complication of chest radiotherapy. It is characterized by decreased ventricular elasticity and distensibility, which can result in decreased ejection fraction, heart failure, and even sudden cardiac death. Pyroptosis, a type of programmed cell death, is mediated by members of the gasdermin (GSDM) family and has been associated with numerous cardiac disorders. The effect of pyroptosis on myocardial fibrosis caused by a combination of radiotherapy and PD-1 inhibitors remains uncertain. In this study, a 6MV X-ray of 20 Gy for local heart irradiation was used in the RIHD mouse model. We noticed that PD-1 inhibitors aggravated radiation-induced cardiac dysfunction and RIMF, concurrently enhancing the presence of CD8 T lymphocytes in the cardiac tissue. Additionally, our findings indicated that the combination of PD-1 inhibitor and thoracic radiation can stimulate caspase-1 to cleave GSDMD, thereby regulating pyroptosis and liberating interleukin-8 (IL-18). In the myocardium of mice, the manifestation of pyroptosis mediated by GSDMD is accompanied by the buildup of proteins associated with fibrosis, such as collagen I, transforming growth factor β1 (TGF-β1), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor α (TNF-α). Moreover, it was discovered that TFG-β1 induced the phosphorylation of Smad2/Smad3 when the cardiac underwent PD-1 inhibitor in conjunction with thoracic irradiation (IR). The findings of this research indicate that PD-1 inhibitor worsen RIMF in mice by triggering GSDMD-induced pyroptosis and influencing the TGF-β1/Smads pathway. While using the caspase-1 inhibitor Z-YVAD-FMK, RIMF can be alleviated. Blocking GSDMD may be a viable strategy for managing myocardial fibrosis caused by the combination of PD-1 inhibitors and radiotherapy.
PubMed: 38773023
DOI: 10.1007/s10753-024-02056-9 -
Bioinformatics and Biology Insights 2024Rheumatoid arthritis (RA) is considered a notable prolonged inflammatory condition with no proper cure. Synovial inflammation and synovial pannus are crucial in the...
BACKGROUND
Rheumatoid arthritis (RA) is considered a notable prolonged inflammatory condition with no proper cure. Synovial inflammation and synovial pannus are crucial in the onset of RA. The "tumor-like" invading proliferation of new arteries is a keynote of RA. Commiphora wightii () is a perennial, deciduous, and trifoliate plant used in several areas of southeast Asia to cure numerous ailments, including arthritis, diabetes, obesity, and asthma. Several investigations have indicated therapeutic efficacy in the treatment of arthritis. However, the precise molecular action is yet unknown.
MATERIAL AND METHODS
In this study, a network pharmacology approach was applied to uncover potential targets, active therapeutic ingredients and signaling pathways in for the treatment of arthritis. In the groundwork of this research, we examined the active constituent-compound-target-pathway network and evaluated that (Guggulsterol-V, Myrrhahnone B, and Campesterol) decisively donated to the development of arthritis by affecting tumor necrosis factor (TNF), PIK3CA, and MAPK3 genes. Later on, docking was employed to confirm the active components' efficiency against the potential targets.
RESULTS
According to molecular-docking research, several potential targets of RA bind tightly with the corresponding key active ingredient of With the aid of network pharmacology techniques, we conclude that the signaling pathways and biological processes involved in had an impact on the prevention of arthritis. The outcomes of molecular docking also serve as strong recommendations for future research. In the context of this study, network pharmacology combined with molecular docking analysis showed that acted on arthritis-related signaling pathways to exhibit a promising preventive impact on arthritis.
CONCLUSION
These results serve as the basis for grasping the mechanism of the antiarthritis activity of . However, further / study is needed to verify the reliability of these targets for the treatment of arthritis.
PubMed: 38765022
DOI: 10.1177/11779322241247634 -
Modern Pathology : An Official Journal... May 2024The EWSR1::PBX3 fusion gene, commonly associated with cutaneous syncytial myoepitheliomas, is also found in myoepithelial tumors (METs) of bone and soft tissue. These...
The EWSR1::PBX3 fusion gene, commonly associated with cutaneous syncytial myoepitheliomas, is also found in myoepithelial tumors (METs) of bone and soft tissue. These tumors typically demonstrate benign histology and favorable outcomes. This study examines 6 previously unreported intraosseous METs harboring the EWSR1::PBX3 fusion, focusing on their histopathologic characteristics, immunophenotype, clinical and radiographic profiles, and patient outcomes. The cohort comprised 5 men and 1 woman, aged 25 to 65 years (median age: 31 years), with tumors located in the proximal tibia (3 cases), distal radius (2 cases), and ilium (1 case) and sizes between 3.2 and 12.2 cm (median size: 3.9 cm). Imaging showed osteolytic lesions with varying degrees of cortical involvement and soft tissue extension in 3 cases. Histologically, 4 tumors showed mainly uniform oval-to-spindled cells in syncytial or fascicular arrangements within a collagenous matrix, displaying either bland nuclear features or mild atypia, and low to slightly elevated mitotic activity (≤1 per 10 high-power fields in 3 cases and 6 per 10 high-power fields in 1), classifying them as benign or atypical METs. In contrast, 2 tumors exhibited pronounced nuclear atypia with ovoid, spindled, epithelioid and round cells, hyperchromatic nuclei, inconspicuous nucleoli, increased N/C ratios, high mitotic rates (17 and 19 per 10 high-power fields), and extensive necrosis. Both tumors behaved aggressively-one patient underwent amputation after neoadjuvant chemotherapy and radiation, and the other died within 7 months with the disease still present. Immunohistochemically, the tumors consistently expressed epithelial membrane antigen and S100 but lacked keratin (AE1/AE3) expression. Our study demonstrated that bone METs with EWSR1::PBX3 fusions encompass a histologic continuum from benign to malignant, with benign/atypical METs mirroring their cutaneous analogs in morphology, and malignant variants distinguished by heterogeneous cytologic and architectural features, pronounced nuclear atypia, and high mitotic rates.
PubMed: 38763423
DOI: 10.1016/j.modpat.2024.100514 -
Dermatology Online Journal Mar 2024Osteonecrosis of the jaw is a recognized complication associated with bevacizumab. Here, we present a patient with squamous cell carcinoma of the tonsil who experienced...
Osteonecrosis of the jaw is a recognized complication associated with bevacizumab. Here, we present a patient with squamous cell carcinoma of the tonsil who experienced minimal skin fibrosis following intensity-modulated radiation therapy. Subsequently, the patient developed rectal adenocarcinoma and encountered osteonecrosis of the jaw after receiving two cycles of bevacizumab. Close monitoring, accompanied by thorough examination to detect early signs of osteonecrosis of the jaw, should be considered for patients who have undergone radiation therapy in the head and neck region and are receiving bevacizumab or other medications known to be associated with osteonecrosis of the jaw.
Topics: Humans; Bevacizumab; Carcinoma, Squamous Cell; Radiotherapy, Intensity-Modulated; Tonsillar Neoplasms; Male; Osteonecrosis; Adenocarcinoma; Rectal Neoplasms; Antineoplastic Agents, Immunological; Middle Aged; Jaw Diseases
PubMed: 38762867
DOI: 10.5070/D330163297 -
Mathematical Biosciences Jul 2024Brain metastases (BMs) are the most common intracranial tumor type and a significant health concern, affecting approximately 10% to 30% of all oncological patients.... (Review)
Review
Brain metastases (BMs) are the most common intracranial tumor type and a significant health concern, affecting approximately 10% to 30% of all oncological patients. Although significant progress is being made, many aspects of the metastatic process to the brain and the growth of the resulting lesions are still not well understood. There is a need for an improved understanding of the growth dynamics and the response to treatment of these tumors. Mathematical models have been proven valuable for drawing inferences and making predictions in different fields of cancer research, but few mathematical works have considered BMs. This comprehensive review aims to establish a unified platform and contribute to fostering emerging efforts dedicated to enhancing our mathematical understanding of this intricate and challenging disease. We focus on the progress made in the initial stages of mathematical modeling research regarding BMs and the significant insights gained from such studies. We also explore the vital role of mathematical modeling in predicting treatment outcomes and enhancing the quality of clinical decision-making for patients facing BMs.
Topics: Humans; Brain Neoplasms; Models, Theoretical; Models, Biological; Mathematical Concepts
PubMed: 38759950
DOI: 10.1016/j.mbs.2024.109207